Targeting PI3K/PTEN/BRAF Pathway in Melanoma

ACT in B6 nude mice, in vivo vaccination, PLX4720 treatment, anti-VEGF blocking antibody treatment, and in vivo Bioluminescence Imaging were performed as previously described (5 (link), 27 (link)). GSK2636771 and BKM120 (Chemie Tek) were suspended in 1% (w/v) methylcellulose and administered to mice daily by oral gavage at a dose of 30mg/kg and 60mg/kg respectively. For the spontaneous tumor model, Tyr:CreER; PTEN^lox/lox; BRAF ^V600E/+ mice on a C57BL/6 background (6–8 weeks of age) were treated with 4-hydroxytamoxifen to induce the expression of Cre as previously described (11 (link)). The anti-mouse PD-1 antibody (29F.1A12, Biolegend) was intraperitoneally injected on days 0, 2 and 4 at a dose of 100 μg/per mouse. The relevant solvent and control rat IgG antibody (Sigma) were administered to control animals.

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Peng W., Chen J.Q., Liu C., Malu S., Creasy C., Tetzlaff M.T., Xu C., McKenzie J.A., Zhang C., Liang X., Williams L.J., Deng W., Chen G., Mbofung R., Lazar A.J., Torres-Cabala C.A., Cooper Z.A., Chen P.L., Tieu T.N., Spranger S., Yu X., Bernatchez C., Forget M.A., Haymaker C., Amaria R., McQuade J.L., Glitza I.C., Cascone T., Li H.S., Kwong L.N., Heffernan T.P., Hu J., Bassett RL J.r., Bosenberg M.W., Woodman S.E., Overwijk W.W., Lizée G., Roszik J., Gajewski T.F., Wargo J.A., Gershenwald J.E., Radvanyi L., Davies M.A, & Hwu P. (2015). Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer discovery, 6(2), 202-216.

Publication 2015

BKM120 control rat IgG antibody

Animals Anti Anti antibody Bkm120 Braf C57bl mice Gavage Gsk2636771 Hydroxytamoxifen Igg antibody Methylcellulose Mouse Nude mice Plx4720 Solvent Tumor Vaccination Vegf

Corresponding Organization : The University of Texas MD Anderson Cancer Center

Other organizations : University of Chicago, Yale University

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Variable analysis

independent variables

ACT in B6 nude mice
PLX4720 treatment
Anti-VEGF blocking antibody treatment
GSK2636771 administered daily by oral gavage at 30mg/kg
BKM120 administered daily by oral gavage at 60mg/kg
4-hydroxytamoxifen to induce Cre expression in Tyr:CreER; PTEN^lox/lox; BRAF^V600E/+ mice
Anti-mouse PD-1 antibody (29F.1A12, Biolegend) administered intraperitoneally on days 0, 2 and 4 at 100 μg/per mouse

dependent variables

In vivo vaccination
In vivo Bioluminescence Imaging

control variables

Relevant solvent control
Control rat IgG antibody (Sigma)

controls

Positive control: None specified
Negative control: Relevant solvent and control rat IgG antibody

Annotations

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